Distribution of Volumes of Individual Glomeruli in Kidneys at Autopsy: Association with Physical and Clinical Characteristics and with Ethnic Group

Abstract

We have demonstrated considerable variability in the volumes of different glomeruli in given individuals (individual glomerular volume: IGV) in a stereologic study of kidneys at forensic autopsy performed to investigate sudden or unexpected death in people without manifest kidney disease. We review some important associations of IGV by subject characteristics and by ethnic groups. IGVs were measured by the Cavalieri method in 30 glomeruli in each of 111 adult males who belonged to 4 ethnic groups, i.e. US Whites, African-Americans, Africans from Senegal, and Australian Aborigines. Correlations of pooled IGV values with certain subject characteristics were evaluated in the US Whites. Pooled IGV data were compared in subjects across the 4 ethnic groups. In US Whites, mean IGV and its variance were greater with higher age, lower nephron number, lower birth weight, and with gross obesity, hypertension and cardiovascular death. In comparisons by ethnic group, mean IGV and IGV ranges were higher in African-Americans and Australian Aborigines than in US Whites and African Senegalese subjects. We conclude that glomerular enlargement with volume heterogeneity marks more advanced age, relative nephron deficiency, lower birth weight, obesity, hypertension, and advanced cardiovascular disease. The findings in African-Americans and Australian Aborigines suggest that larger IGVs and volume heterogeneity might mark populations with accentuated susceptibility to hypertension and kidney disease, but the data need to be further examined in the context of the determining characteristics defined in the US Whites.

Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease

“…Like total nephron number, mean glomerular volume was found to vary up to 10-fold in the Monash Series of 420 kidneys of subjects from five ethnic groups 51 . Total nephron number consistently varies inversely with mean glomerular volume 13 .…”

APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults

“…Furthermore, a recent study describes the influence of APOL1 risk variants on enhanced podocyte necrosis through compromised lysosomal membrane permeability. 23 Much remains to be explored in this area, including, the full degree of heterogeneous individual glomerular enlargement that the estimate of average V glom disguises, 17,24 and indices of podocyte number and density in the younger and older at-risk subjects 25 in the various APOL1 subgroups. This series is not a resource for the study of kidney disease, because such subjects were deliberately excluded.…”

“…Furthermore, the use of V glom , which is an average value of glomerular volumes for a given kidney, provides no indication the variability in volumes of individual glomeruli within a given subject. 13,[16][17][18]24 An additional caution is the inference that data on different people at different ages on a cross-sectional study necessarily represent probable changes in an individual followed over a lifetime.…”

“…[13][14][15] Moreover, our studies on individual glomerular volumes showed more size heterogeneity and net enlargement in African Americans than in non-African Americans. [16][17][18] The intent of the autopsy series in which this study is nested was to examine microanatomy in normal kidneys. Here we describe histomorphometric phenotype in adult African-American subjects in that series according to their APOL1 risk allele profiles.…”

Nephron Hypertrophy and Glomerulosclerosis and Their Association with Kidney Function and Risk Factors among Living Kidney Donors

“…Autopsy studies allow assessment of renal morphology in relation to CKD risk factors (16), but are typically of small sample size and are reflective of substantial disease burden at the time of death. Autopsy studies can be restricted to accidental deaths to be more reflective of the general population, but kidney function and CKD risk factors are not known at the time of an unexpected death.…”